Development of Nasal Mucoadhesive In Situ Gel Spray Formulations for Antiviral Purpose


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Özkan B., Altuntaş E., Çalık H., Erginer Y., Çakır Koç R.

IV. INTERNATIONAL AGRICULTURAL, BIOLOGICAL &LIFE SCIENCECONFERENCE, Edirne, Turkey, 22 - 31 August 2022, pp.197

  • Publication Type: Conference Paper / Summary Text
  • City: Edirne
  • Country: Turkey
  • Page Numbers: pp.197
  • Istanbul University Affiliated: Yes

Abstract

INTRODUCTION

The respiratory system is in dynamic contact with the atmosphere until the person's last breath (1). Viral agents commonly enter the body through the respiratory tract and cause infections. In studies on respiratory tract infections; influenza A, influenza B, rhinovirus (RV), respiratory syncytial virus (RSV), coronaviruses are among the viruses that are frequently encountered as viral agents (2). In this study, it was aimed to develop antiviral in situ mucoadhesive spray formulations with protective activity to prevent viruses from causing disease in the body by settling in the respiratory system through the nasal route. For this purpose, the broad spectrum potent antiviral “18β-Glycyrrhetinic acid (GA)”, which is the main active ingredient of licorice root extract, was used in formulations.

METHODS

Various formulations have been prepared using gellan gum (DGG) which provides in situ gelling, and different mucoadhesive polymers such as hydroxypropyl methylcellulose (HPMC), sodium carboxymethyl cellulose (Na-CMC), xanthan gum, Carbopol® 974P NF with biodegradability, good solubility in water and good release properties.

In order to determine the proper in situ gel formulation; rheological properties, mechanical properties, and mucoadhesive strength of the formulations were investigated. In addition; in vitro gelling capacity, ex vivo mucoadhesion strength, water holding capacity, sprayability, and in vitro cytotoxicity were also studied.

RESULTS

As a result, it was concluded that the formulation containing 0.5% DGG and 0.5% CMC polymers showed optimum properties. This in situ gel formulation has a clear appearance with uniform sprayability. When it was mixed with simulated nasal fluid at 34°C, its viscosity increased significantly to form a clear gel. According to the data of texture profile analysis, it was determined that it had higher adhesiveness (0.560 mJ) compared to other formulations. Similarly, in the rheological synergism study performed with mucin solution, the mucoadhesive strength (9.53 Pa) was found to be higher. In the ex vivo mucoadhesion test, it has the highest mucoadhesion strength (19.67 g) after the formulation containing 0.7% CMC. The formulation containing 0.7% CMC was eliminated due to improper sprayability pattern. Considering all the criteria, it was decided to continue further studies with the formulation containing 0.5% DGG + 0.5% CMC which has the desired properties.

According to the results of in vitro cytotoxicity study with the active substance, it didn't cause any significant decrease in cell viability at concentrations between 4 and 80 µg/ml. No reduction in cell viability was observed at all tested concentrations between 4 and 60 µg/ml. A concentration of 80 µg/ml (p < 0.05) slightly reduced cell viability to 87.90% which is evaluated as non-toxic according to ISO 10993-5:2009 standard.

CONCLUSION

It is considered that the developed mucoadhesive in situ gel can provide a great benefit in protecting individuals from viral infections and can also be a potential product to meet the need for protection against viral agents. Thus, it will be easier to control the spread rate of viral infections and contribute to reducing the negative impact.